Dataset Information

Association of HLA-DRA and IL2RA Polymorphisms with the Severity and Relapses Rate of Multiple Sclerosis in an Iranian Population.

ABSTRACT: Background:Multiple sclerosis (MS) is a multifactorial condition in which many genetic and environmental factors interfere. The association between genes involved in the immune system and MS was previously reported. The aims of this study were to evaluate 14 SNPs of HLA-DRA, 14 SNPs of IL2RA with severity of MS through Expanded Disability Status Scale (EDSS) and Annualized Relapse Rate (ARR). Methods:102 patients with MS referred to Sina hospital in Tehran, Iran, were diagnosed and studied based on McDonald's guideline, clinical signs, and brain imaging procedures. All patients were included in the study following informed consent. Genotyping study of 14 variants in the HLA-DRA, and 14 variants in IL2RA was conducted by Sanger sequencing. Disease outcomes including EDSS and ARR were registered. Outcome measures between different genotypes of each SNPs were compared separately. Results:Among 14 SNPs in IL 2RA the genotypes of rs12722489 showed a significant association with ARR in two consecutive years. Mean ARR1 was 1.06±1.12, 0.20±0.34 and 0.31±.50 for AA, GA, and GG genotypes, respectively (p value= 0.008). Mean ARR2 was 1.5±1.08, 0.28±0.40, and 0.42±0.55 for AA, GA, and GG, respectively (p value= 0.001). Regression analysis showed a significant association between rs12722489 with ARR1 and ARR2, removing the potential confounding mediators. No significant association was found between SNPs in HLA-DRA with the attack rate and severity of MS. Conclusion:The rs12722489 of IL-2RA has an association with ARR, but not with EDSS.

SUBMITTER: Asouri M

PROVIDER: S-EPMC7603254 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Association of <i>HLA-DRA</i> and <i>IL2RA</i> Polymorphisms with the Severity and Relapses Rate of Multiple Sclerosis in an Iranian Population.

Asouri Mohsen M Alinejad Rokni Hamid H Sahraian Mohammad Ali MA Fattahi Sadegh S Motamed Nima N Doosti Rozita R Amirbozorgi Galia G Karimpoor Morteza M Mahboudi Fereidoun F Akhavan-Niaki Haleh H

Reports of biochemistry & molecular biology 20200701 2

<h4>Background</h4>Multiple sclerosis (MS) is a multifactorial condition in which many genetic and environmental factors interfere. The association between genes involved in the immune system and MS was previously reported. The aims of this study were to evaluate 14 SNPs of <i>HLA-DRA</i>, 14 SNPs of <i>IL2RA</i> with severity of MS through Expanded Disability Status Scale (EDSS) and Annualized Relapse Rate (ARR).<h4>Methods</h4>102 patients with MS referred to Sina hospital in Tehran, Iran, wer ...[more]

PMID: 33178861

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Project description:Major histocompatibility complex class II (MHC-II) genes are fundamental components that contribute to adaptive immune responses. While characterization of the chromatin features at the core promoter region of these genes has been studied, the scope of histone modifications and the modifying factors responsible for activation of these genes are less well defined. Using the MHC-II gene HLA-DRA as a model, the extent and distribution of major histone modifications associated with active expression were defined in interferon-? induced epithelial cells, B cells, and B-cell mutants for MHC-II expression. With active transcription, nucleosome density around the proximal regulatory region was diminished and histone acetylation and methylation modifications were distributed throughout the gene in distinct patterns that were dependent on the modification examined. Irrespective of the location, the majority of these modifications were dependent on the binding of either the X-box binding factor RFX or the class II transactivator (CIITA) to the proximal regulatory region. Importantly, once established, the modifications were stable through multiple cell divisions after the activating stimulus was removed, suggesting that activation of this system resulted in an epigenetic state. A dual crosslinking chromatin immunoprecipitation method was used to detect histone modifying protein components that interacted across the gene. Components of the MLL methyltransferase and GCN5 acetyltransferase complexes were identified. Some MLL complex components were found to be CIITA independent, including MLL1, ASH2L and RbBP5. Likewise, GCN5 containing acetyltransferase complex components belonging to the ATAC and STAGA complexes were also identified. These results suggest that multiple complexes are either used or are assembled as the gene is activated for expression. Together the results define and illustrate a complex network of histone modifying proteins and multisubunit complexes participating in MHC-II transcription.

Dataset Information

Association of HLA-DRA and IL2RA Polymorphisms with the Severity and Relapses Rate of Multiple Sclerosis in an Iranian Population.

Publications

Association of <i>HLA-DRA</i> and <i>IL2RA</i> Polymorphisms with the Severity and Relapses Rate of Multiple Sclerosis in an Iranian Population.

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